Senescent liver cells release a senescence-associated secretory phenotype (SASP) that disrupts liver homeostasis and accelerates chronic disease progression across metabolic fatty liver disease, viral hepatitis, fibrosis, and hepatocellular carcinoma. These permanently growth-arrested cells, triggered by DNA damage and telomere shortening, create inflammatory microenvironments that fuel pathogenesis. The findings highlight senescence as a unifying mechanism underlying diverse liver pathologies, representing a paradigm shift from viewing aging as merely cumulative damage to recognizing active cellular programs driving disease. This mechanistic understanding opens promising therapeutic avenues through senolytic drugs that selectively eliminate senescent cells, potentially reversing disease progression rather than just managing symptoms. The dual nature of senescence—protective in acute settings but harmful when chronic—suggests timing will be critical for interventions. Combination approaches pairing senolytics with existing antiviral, antifibrotic, and immunotherapies could amplify treatment efficacy. However, translating these insights requires standardized evaluation systems and reliable biomarkers to identify senescent cell burden in patients, challenges that currently limit clinical application of this emerging therapeutic strategy.